Transmembrane protein 45b in peripheral sensory neurons selectively mediates IL-31-dependent chemical itch.

PURPOSE: We previously identified transmembrane protein 45b (Tmem45b) as a pain-related molecule essential for mechanical pain hypersensitivity but not for thermal pain hypersensitivity. A subset of Tmem45b is expressed in TRPV1-positive primary afferents, which are specialized in transmitting thermal pain and specific types of itch. Here, we examined the involvement of Tmem45b in itch perception. METHODS: Behavioral experiments using Tmem45b knockout mice and wild-type mice were conducted to assess the role of Tmem45b in acute and chronic itch mediated by TRPV1-positive primary afferents. In addition, histochemical analyses were performed to identify Tmem45b-positive neurons in itch transmission. Similarly, chronic itch models induced by 2.4-dinitrofluorobenzene and imiquimod showed no significant differences between KO and WT mice. Histochemical analysis revealed that approximately 70% of dorsal root ganglion neurons that were double positive for Tmem45b mRNA and TRPV1 also expressed IL-31 receptor mRNA. Additionally, approximately 30% of dorsal root ganglion neurons that were double positive for Tmem45b mRNA and TRPV1 were also positive for natriuretic polypeptide B mRNA, a marker of pruriceptive afferents, suggesting their involvement in itch transmission. CONCLUSION: These findings demonstrate that Tmem45b is selectively involved in IL-31-induced chemical itch and suggest that Tmem45b could serve as a novel modulator for IL-31-induced itch.